Effects on GLP-1, PYY, and leptin by direct stimulation of terminal ileum and cecum in humans: implications for ileal transposition

Background: We do not have a unified, scientifically tested theory of causation for obesity and its co-morbidities, nor do we have explanations for the mechanics of the metabolic/bariatric surgery procedures. Integral to proffered hypotheses are the actions of the hormones glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and leptin. The objective of this study was to obtain blood levels of GLP-1, PYY, and leptin after stimulation of the terminal ileum and cecum by a static infusion of a food hydrolysate in morbidly obese patients undergoing a duodenal switch procedure.

Setting: University Hospital.

Methods: Plasma levels of GLP-1, PYY, and leptin were obtained at 0, 30, 60, 90, and 120 minutes after instillation of 240 mL of a food hydrolysate into the ileum or cecum.

Results: The mean±SD GLP-1 values by cecal stimulation for 0, 30, 60, 90, and 120 minutes were: 41.3±23.2; 39.6±21.8; 38.9±19.1; 47.4±22.3; 51.7±27.3 pM, and by ileal stimulation: 55.0±32.8; 83.4±16.1; 78.7±23.8; 84.7±23.5; 76.4±25.6. The mean±SD PYY values by cecal stimulation were: 62.1±24.8; 91.1±32.8; 102.1±39.6; 119.6±37.5; 130.3±36.7, and by ileal stimulation: 73.8±41.6; 138.1±17.7; 149.5±23.3; 165.7±24.3; 155.5±29.1. Percent change in PYY levels increased ~150%, GLP-1 increased ~50%, and leptin decreased ~20%.

Conclusion: Direct stimulation of the human terminal ileum and cecum by a food hydrolysate elicits significant plasma GLP-1 and PYY elevations and leptin decreases, peaking at 90-120 minutes. The ileal GLP-1 and PYY responses exceed those of the cecum, and the PYY effect is about 3-fold that of GLP-1. The results of this study question the satiety premise for ileal transposition.